The transformation of cultuled mammalian cells with defined DNA fragments has been explored as a system for studying eukaryotic gene regulation with a special interest in studying the expression of normal human globin genes. The co-transformation of mouse fibroblasts with herpes simplex thymidine kinase gene and a recombinant bacteriophage, lambdaHbetaG1, containing both the human delta and beta globin genes has resulted in mouse cell lines in which the human globin genes are stably integrated without apparent rearrangement. The human globin genes in transformed mouse fibroblasts were found to be virtually unmethylated. Although undermethylation of DNA seems to correlate with gene activity in normal cells, the level of expression of human globin genes in the co-transformed mouse fibroblasts was much less than that found in human erythroblasts. Nor does undermethylation insure correct transcription since the 75-100 copies of human beta globin mRNA found in each cell were seemingly somewhat shorter than the authentic mRNA species.